The molecular mechanisms regulating oncogenic signalling by sphingosine kinase 1 phosphorylation and localisation

点击翻译按钮获取中文摘要

Sphingosine kinase is an enzyme that produces the lipid signalling molecule, sphingosine phosphate that is involved in the regulation of a diverse array of important mammalian cellular functions. Studies have found that sphingosine kinase is involved in enhancing the growth and survival of cells. Disregulation of sphingosine kinase is involved in tumorigenesis, and if its activity can be blocked, tumor size can be reduced. Therefore, this provides a potential target for therapeutic intervention in cancer. However, the manner by which cells regulate sphingosine kinase is not well known. It is known that phosphorylation of sphingosine kinase increases the activity of this enzyme, and also causes a shift in its localisation the the plasma membrane. We have found that both of these processes are essential for the tumorigenic effects of sphingosine kinase, but very little is known about how these processes are achieved in the cell. This study will investigate this problem with the view that understanding these processes will assist in the development of new drugs to block the tumorigenic effects of sphingosine kinase.